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Biomedical subjects

C Ma

Publications and source records attributed to C Ma.

At least 37 records · Page 2Linked to original sources
PubMed2001

Expression of matrix metalloproteinase (MMP-1) and tissue inhibitor of MMP in serosal tissue of intraperitoneal organs and adhesions.

OBJECTIVE: To compare expression of matrix metalloproteinase (MMP-1) and tissue inhibitor of MMP (TIMP-1) in serosal tissue of intraperitoneal organs and adhesions. DESIGN: Prospective and cross-sectional study. SETTING: Academic research centers. PATIENT(S): Patients undergoing abdominal or pelvic surgery. INTERVENTION(S): MMP-1 and TIMP-1 expression. MAIN OUTCOME MEASURE(S): Expression of messenger ribonucleic acid (mRNA) and protein was measured by using quantitative reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay. RESULT(S): Serosal tissue of intraperitoneal organs and adhesions express MMP-1 and TIMP-1 mRNA and protein at levels that are consistently varied with 10- to 10,000-fold and 2- to 10-fold higher TIMP, mRNA and protein, respectively. Parietal peritoneum, fallopian tubes and ovaries express higher MMP-1 mRNA levels compared with uterus and adhesions; the lowest expression is found in small and large bowels, subcutaneous tissue. and omentum. Expression of TIMP-1 mRNA was less variable; the highest level was found in the uterus and the lowest in subcutaneous tissue and small bowels. There was less variability in MMP-1 and TIMP-1 protein content than mRNA expression; ovaries and adhesions contained the highest MMP-1 and TIMP-1 levels, respectively, and peritoneum contained the lowest. The MMP-1 and TIMP-1 content and ratios further indicate limited MMP-1 proteolytic activity. Although tissues from premenopausal women express more MMP-1 and TIMP-1, expression did not differ by sex or age. CONCLUSION(S): Because MMP-1 and TIMP-1 expression varies consistently among the serosal tissues of peritoneal organs and adhesions, and because tissue injury alters their expression, site-specific variations in expression of these substances may predispose a particular organ to develop more adhesions.

Abdomen↗
PubMed2001

Immune related genetic polymorphisms and schizophrenia among the Chinese.

Genetic association studies were conducted among two independent cohorts of Chinese ethnicity. The samples consisted of cases and unrelated controls, ascertained from Guangzhou, China, and Singapore. The studies were prompted by our earlier report of an association between schizophrenia and HLA DQB1 alleles (HLA DQB1*0602 and HLA DQB1*0303) in the Singapore sample. Polymorphisms of HLA DQB1 and flanking markers on chromosome 6p21.3 were investigated in the first part of the study. A significant negative association with HLA DQB1*0402 was detected in the Guangzhou sample (Odds ratio, OR 0.26, 95% confidence intervals, CI 0.1, 0.6; p < 0.02, corrected for multiple comparisons). Additional analysis of the Guangzhou and Singapore samples revealed associations at three other anonymous markers flanking HLA DQB1. In the second part of the study, three polymorphisms at the Interleukin-1 gene cluster (IL-1, chromosome 2q13-q21) were investigated in both cohorts, since associations with schizophrenia have been reported in another sample. Persuasive evidence for an association at IL-1 was not detected in either sample. Our results suggest a susceptibility locus for schizophrenia in the HLA region among the Chinese, but further clarification is necessary.

Adult↗
PubMed2001

Stat6 dependent goblet cell hyperplasia during intestinal nematode infection.

To identify the role of signal transducer and activator of transcription factor 6 (Stat6) in the development of intestinal goblet cell hyperplasia during nematode infection, we compared the number of goblet cells in Stat6 deficient (Stat6 -/-) mice with that generated in wild-type (Stat6 +/+) mice in Trichinella spiralis infection. The number of goblet cells significantly increased with infection in wild-type mice. However, Stat6 -/- failed to generate infection-induced goblet cell hyperplasia and a significantly lower number of goblet cells was observed in Stat6 -/- mice on days 14 and 21 postinfection compared to Stat6 +/+ mice. In addition to suppressed goblet cell numbers, Stat6 -/- mice exhibited severe impairment in their ability to produce IL-4 and IL-13 and to expel the parasites from the gut. Our study clearly shows an essential role of Stat6 in intestinal goblet cell hyperplasia which accompanies this infection. We postulate that Th2 cytokines regulate the development of goblet cell hyperplasia in gut during nematode infection via Stat6 activation and that the increased number of goblet cells plays an important role in host protective immunity against the infection.

Animals↗
PubMed2001

A comprehensive account on the role of efflux transporters in the gastrointestinal absorption of 13 commonly used substrate drugs in humans.

BACKGROUND: The potential absorption-limiting effect of intestinal efflux transporters such as P-glycoprotein (P-gp) has been well recognized, primarily based on results of numerous Caco-2 cell studies showing that flux, permeability, or transport clearance of drugs from the basolateral to the apical (B --> A) compartment is greater than that from the apical to the basolateral (A --> B) compartment. Except for very limited examples such as celiprolol, talinolol, pafenolol and paclitaxel, the potential clinical impact of these transporters on oral absorption of the vast number of commonly prescribed drug substrates in humans has not been closely examined to date. OBJECTIVE: To evaluate whether these efflux transporters may play a significant role in limiting oral absorption of 13 commonly used drugs (digoxin, etoposide, felodipine, fexofenadine, furosemide, indinavir, losartan, nadolol, propranolol, ritonavir, saquinavir, tacrolimus, and verapamil) in humans. METHODS: Drug absorption properties such as the rate (as judged by the Cmax and tmax) and extent (as judged by AUC or urinary excretion of drugs) of absorption as a function of dose, as well as the completeness of oral absorption were obtained from the literature. RESULTS: The absorption properties of these 13 drugs are not consistent with absorption-retarding expectations from in vitro studies because they all show apparent dose-independent kinetics in absorption or bioavailability and completeness of oral absorption is shown for most of the drugs evaluated. CONCLUSIONS: In spite of being substrates of intestinal efflux transporters such as P-gp, the in vivo oral absorption of 13 drugs examined apparently is not significantly impeded by efflux transporters. Thus, there may exist an apparent discrepancy between in vitro "expectations" and in vivo results; potential reasons for this are discussed. The present findings, however, do not de-emphasize potential in vivo importance of efflux transporters in affecting (increasing or decreasing) oral absorption of certain substrate drugs, especially those with low to moderate intestinal permeability and with low therapeutic index, or the importance of efflux transporters in the study of mechanisms of drug absorption and some potentially clinically significant drug-drug and drug-food interactions.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Zolpidem, triazolam, and diazepam decrease distress vocalizations in mouse pups: differential antagonism by flumazenil and beta-Carboline-3-carboxylate-t-butyl ester (beta-CCt).

In response to stressful events, neonatal mice emit ultrasonic vocalizations (USVs), which are suppressed by BZ agonists. The present study examined the role of the benzodiazepine/alpha1 (BZ/alpha1) receptor subtype in the suppression engendered by the BZ/alpha1-preferring agonist zolpidem and the nonselective BZ agonists triazolam and diazepam. The role of BZ receptor subtypes was explored further by conducting antagonism studies using the BZ/alpha1-preferring antagonist beta-carboline-3-carboxylate-t-butyl ester (beta-CCt), in comparison with the nonselective BZ antagonist flumazenil. Mouse pups (CFW strain) were separated from their dam and littermates at day 7, and placed for 4 min in a test chamber with reduced ambient temperature (19 +/- 1 degrees C) for recording USVs, motor incoordination (measured as a pup rolling on its back per grid cross), and body temperature. Zolpidem, triazolam, and diazepam suppressed USVs in a dose-dependent manner, concomitant with increases in incoordination and augmentation of hypothermia. These effects of the three BZ agonists were blocked by flumazenil in a manner consistent with surmountable antagonism. The ability of zolpidem, but not triazolam or diazepam, to suppress USVs and augment hypothermia was antagonized by beta-CCt, whereas the increase in motor incoordination engendered by zolpidem, triazolam, and diazepam was not sensitive to beta-CCt administration. Collectively, these results suggest that zolpidem suppresses distress USVs in mouse pups by a mechanism distinct from that of typical BZs. Furthermore, suppression of distress USVs by zolpidem may involve BZ/alpha1 receptors and a nonanxiolytic mechanism, such as hypothermia.

Animals↗
PubMed2001

[No evidence for association between the alpha 2-macroglobulin polymorphism and Alzheimer's disease in the Han Chinese].

OBJECTIVE: To determine the effect of the pentanucleotide deletion polymorphism adjacent to a consensus splice site in intron 17 of alpha 2-macroglobulin(A2M) gene on the development of late-onset Alzheimer's disease (LOAD) in the Han Chinese in Guangzhou area. METHODS: A2M and apolipoprotein E genotypes were examined by polymerase chain reaction(PCR) and restriction fragment length polymorphism (RFLP) techniques in the patients(32 men and 65 women) with LOAD and age-matched healthy elderly Chinese subjects (57 men and 54 women). RESULTS: The A2M gene deletion allele frequency was 2.6% in the cases with LOAD and 2.7% in the controls. In the LOAD cases, the frequency of apoE-epsilon4 increased significantly (Z=3.32, P<0.01). ApoE-epsilon4 was associated with LOAD (RR=2.67, chi(2)=10.71, P<0.01) while the A2M deletion polymorphism was not associated with LOAD even the samples were stratified according to the presence of the apoE-epsilon4 allele. CONCLUSION: The above data demonstrate that there is no evidence for the association of A2M polymorphism with the development of LOAD in the Han Chinese population in Gaungzhou.

Alzheimer Disease↗
PubMed2001

[Preliminary assessment of articles reporting cancer diagnostic tests].

OBJECTIVE: To improve the quality of papers on clinical diagnostic tests. METHODS: Articles of diagnostic tests published in the Chinese Journal of Oncology in the year 1990 were surveyed by cluster sampling method. RESULTS: In the 23 articles surveyed, immunoassays constituted the largest category, accounting for 39.1% (9/23), followed by biochemical markers and radiological tests, accounting for 17.4% (4/23) and 13.0%(3/23), respectively. Of the 23 articles, 19 (82.6%) employed a well-defined "gold standard", 14 (60.9%) correctly calculated sensitivity and specificity. The interpretation of the test was stated to be "blind" in only 39.1%(9/32). In only one paper were all the seven methodologic criteria adhered. Less than 60% of the articles followed more than four of the seven methodologic criteria, and in 2 articles only one of the criteria was met with. CONCLUSION: Although due attention has been paid to the methodologic criteria of assessing diagnostic tests, the quality of the articles surveyed needs to be improved.

Diagnostic Tests, Routine↗
PubMed2001

Clinical characteristics and basic research development of Peutz-Jeghers syndrome.

OBJECTIVE: To improve clinical knowledge of Peutz-Jeghers syndrome. METHODS: Eight patients with Peutz-Jeghers syndrome from 1984 to 1998 in our hospital were retrospectively reviewed and analyzed in the present study. RESULT: The result of this analysis showed that there were 4 patients appeared with family histories of Peutz-Jeghers syndrome. All of the included patients admitted to the hospital with various complications, and eventually received surgical interventions for these complications, among which, 6 of them had intestinal obstructions mostly (5/6) due to small bowel intussusception, and 2 of them suffered with hemafecia. Post-operative recoveries were generally satisfactory with zero mortality. CONCLUSION: Peutz-Jeghers syndrome is an uncommon digestive dominant hereditary disease. The diagnosis of it with history, symptoms, signs, and proper examinations usually is not difficult Surgical interventions are necessary once complications occur.

Adolescent↗
PubMed2000

Activation of heterotrimeric G-protein signaling by a ras-related protein. Implications for signal integration.

Utilizing a functional screen in the yeast Saccharomyces cerevisiae we identified mammalian proteins that activate heterotrimeric G-protein signaling pathways in a receptor-independent fashion. One of the identified activators, termed AGS1 (for activator of G-protein signaling), is a human Ras-related G-protein that defines a distinct subgroup of the Ras superfamily. Expression of AGS1 in yeast and in mammalian cells results in specific activation of Galpha(i)/Galpha(o) heterotrimeric signaling pathways. In addition, the in vivo and in vitro properties of AGS1 are consistent with it functioning as a direct guanine nucleotide exchange factor for Galpha(i)/Galpha(o). AGS1 thus presents a unique mechanism for signal integration via heterotrimeric G-protein signaling pathways.

Amino Acid Sequence↗
PubMed2000

A beta1,3-glucan recognition protein from an insect, Manduca sexta, agglutinates microorganisms and activates the phenoloxidase cascade.

Pattern recognition proteins function in innate immune responses by binding to molecules on the surface of invading pathogens and initiating host defense reactions. We report the purification and molecular cloning of a cDNA for a 53-kDa beta1,3-glucan-recognition protein from the tobacco hornworm, Manduca sexta. This protein is constitutively expressed in fat body and secreted into hemolymph. The protein contains a region with sequence similarity to several glucanases, but it lacks glucanase activity. It binds to the surface of and agglutinates yeast, as well as gram-negative and gram-positive bacteria. Beta1,3-glucan-recognition protein in the presence of laminarin, a soluble glucan, stimulated activation of prophenoloxidase in plasma, whereas laminarin alone did not. These results suggest that beta1,3-glucan-recognition protein serves as a pattern recognition molecule for beta1,3-glucan on the surface of fungal cell walls. After binding to beta1,3-glucan, the protein may interact with a serine protease, leading to the activation of the prophenoloxidase cascade, a pathway in insects for defense against microbial infection.

Amino Acid Sequence↗
PubMed2000

Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.

Adult↗
PubMed2000

Pharmacophore/receptor models for GABA(A)/BzR subtypes (alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2) via a comprehensive ligand-mapping approach.

Pharmacophore/receptor models for three recombinant GABA(A)/BzR subtypes (alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2) have been established via an SAR ligand-mapping approach. This study was based on the affinities of 151 BzR ligands at five distinct (alpha1-3,5,6beta3gamma2) recombinant GABA(A)/BzR receptor subtypes from at least nine different structural families. Examination of the included volumes of the alpha1-, alpha5-, and alpha6-containing subtypes indicated that region L(2) for the alpha5-containing subtype appeared to be larger in size than the analogous region of the other receptor subtypes. Region L(Di), in contrast, appeared to be larger in the alpha1 subtype than in the other two subtypes. Moreover, region L(3) in the alpha6 subtype is either very small or nonexistent in this diazepam-insensitive subtype (see Figure 16 for details) as compared to the other subtypes. Use of the pharmacophore/receptor models for these subtypes has resulted in the design of novel BzR ligands (see 27) selective for the alpha5beta3gamma2 receptor subtype. alpha5-Selective ligand 27 when injected directly into the hippocampus did enhance memory in one paradigm (Bailey et al., unpublished observations); however, systemic administration of either 9 or 27 into animals did not provide an observable enhancement. This result is in complete agreement with the observation of Liu (1996). It has been shown (Liu, 1996; Wisden et al., 1992) that in the central nervous system of the rat (as well as monkeys and pigeons) there are several native subtypes of the GABA(A) receptor which exhibit different functions, regional distributions, and neuronal locations. Although 27 binds more potently at alpha5beta3gamma2 receptor subtypes and is clearly an inverse agonist (Liu et al., 1996; Liu, 1996), it is possible that this ligand acts as an agonist at one or more subtypes. Liu (1996) clearly showed that a number of imidazobenzodiazepines were negative modulators at one subtype and agonists at another. Therefore, selectivity for a particular subtype at this point is not sufficient to rule out some physiological effect at other GABA(A)/BzR subtypes. The inability of 27 to potentiate memory when given systemically is again in support of this hypothesis, especially since alpha1beta2gamma2 subtypes are distributed throughout the brain (Wisden et al., 1992). A drug delivered systemically is far more likely to interact with all subtypes than one delivered to a specific brain region. This observation (systemic vs intrahippocampal) provides further support for the design of more subtype-specific ligands at the BzR to accurately define their pharmacology, one key to the design of new drugs with fewer side effects.

Animals↗
PubMed2000

Three-dimensional solid-state NMR spectroscopy is essential for resolution of resonances from in-plane residues in uniformly (15)N-labeled helical membrane proteins in oriented lipid bilayers.

Uniformly (15)N-labeled samples of membrane proteins with helices aligned parallel to the membrane surface give two-dimensional PISEMA spectra that are highly overlapped due to limited dispersions of (1)H-(15)N dipolar coupling and (15)N chemical shift frequencies. However, resolution is greatly improved in three-dimensional (1)H chemical shift/(1)H-(15)N dipolar coupling/(15)N chemical shift correlation spectra. The 23-residue antibiotic peptide magainin and a 54-residue polypeptide corresponding to the cytoplasmic domain of the HIV-1 accessory protein Vpu are used as examples. Both polypeptides consist almost entirely of alpha-helices, with their axes aligned parallel to the membrane surface. The measurement of three orientationally dependent frequencies for Val17 of magainin enabled the three-dimensional orientation of this helical peptide to be determined in the lipid bilayer.

Animals↗
PubMed2000

Lanthanide ions bind specifically to an added "EF-hand" and orient a membrane protein in micelles for solution NMR spectroscopy.

Twelve amino acid residues corresponding to an "EF-hand" calcium-binding site were added to the N-terminus of a protein, providing a specific lanthanide ion binding that weakly orients the protein in solution. A comparison of spectra of the protein with and without the EF-hand residues demonstrates that the structure of the native protein is not perturbed by this modification, since there are minimal chemical shift changes. With a lanthanide but not calcium bound to the EF-hand, the protein is weakly oriented by the magnetic field, since residual dipolar couplings can be measured. Since the signs and magnitudes of the couplings varied with the type of lanthanide, this demonstrated the ability to obtain multiple orientations of the protein in solution. The sample is a membrane protein in lipid micelles that disrupted the commonly employed bicelle and filamentous phage solutions; therefore, the addition of a specific metal binding site in the form of an EF-hand may provide a general approach to orienting proteins where the addition of external agents is problematic. An additional benefit is that the lanthanide ions perturb the protein resonances in ways that provide unique orientational and distance constraints.

Amino Acid Sequence↗
PubMed2000

Collagen-embedded platelet-derived growth factor DNA plasmid promotes wound healing in a dermal ulcer model.

BACKGROUND: Gene therapy has shown limited efficacy for treating congenital diseases, partly due to temporary gene expression and host immune responses. Such results suggest that gene therapy is ideal for chronic wound treatment where limited duration of target gene expression is required. This study tested the wound healing effects of topically applied platelet-derived growth factor (PDGF)-A or -B chain DNA plasmids embedded within a collagen lattice. MATERIALS AND METHODS: Four 6-mm dermal ulcer wounds were created in the ears of young adult New Zealand White rabbits made ischemic by division of the central and rostral arteries. Wounds were treated with lyophilized collagen containing PDGF-B DNA (1.0-3.0 mg), PDGF-A DNA (1.0 mg), irrelevant DNA (1.0 mg), or collagen alone. Wounds were dressed and harvested after 10 days for measurement of granulation tissue formation, epithelialization, and wound closure. Results were evaluated with a paired two-tailed Student t test, with P values < 0.05 considered significant. RESULTS: PDGF-B DNA increased new granulation tissue (NGT) formation up to 52% and epithelialization 34% compared with controls. Wound closure was increased up to threefold. At 1.0 mg DNA, PDGF-A and PDGF-B stimulated similar responses. No difference in NGT or epithelialization was seen between control groups. CONCLUSIONS: PDGF DNA gene therapy is effective at accelerating wound healing in ischemic dermal ulcers and provides a viable alternative to peptide growth factor therapy.

Animals↗